Toxicity is a major problem in the chemotherapy of cancer. The existence of circadian chronobiological fluctuations in host toxicity is well established from work in chronopharmacology and chronotoxicology. There are significantly different responses to drugs at different times in the circadian time structure, i.e. hours of changing responsiveness or susceptibility. Can knowledge of some of the chronobiological characteristics of normal and tumor tissue be effectively used to treat tumor bearing hosts with maximal toxicity to the tumor and minimal toxicity to the host's normal tissues? Our main objectives are: (1) Quantitate and analyze rhythmic fluctuations in H3-thymidine uptake (total and incorporated) and mitotic index in corneal and duodenal epithelium, bone marrow and tumor (L 1210, Lewis lung carcinoma, mammary carcinoma and Ehrlich ascites carcinoma) in non-tumor bearing and tumor bearing mice. The specific questions asked are, (a) what are the characteristics of the normal rhythms? (b) do the normal rhythms undergo any changes under the influence of a growing tumor? (c) does the tumor itself demonstrate any rhythmic fluctuations? (2) Identify the times of host resistance and susceptibility to 3 different chemotherapeutic agents (cyclophosphamide, cytosine arabinoside and actinomycin D) in non-tumor bearing and tumor bearing hosts. The question asked is what is the resistance-susceptibility cycle to a chemotherapeutic agent in normal and tumor bearing hosts? (3) Using the data obtained from objectives 1 and 2, our third objective is to use chronotherapy in the chemotherapeutic attack on several different tumors with different chemotherapeutic agents. This chronotherapy will begin with single and multiple dose schedules at the time of most host resistance (or most tumor susceptibility). This approach also includes a sinusoidal dose schedule in which the highest doses are given at the times of maximum resistance and the lowest doses at the times of maximum susceptibility. The goal is to cure or at least significantly lengthen mean survival time with chronotherapy.